You might already be aware that iTunes modifies any ePub files that it transfers to a device, by adding its own metadata file (
iTunesMetadata.plist) into the ePub container. Epubcheck version 1.1. issues warnings when validating such modified files, because the files present in the ePub no longer match the manifest in the
content.opf file. While I think the iTunes developers were extraordinarily rude in silently modifying user files in this way, in practice I have to admit that it’s hardly a game-breaker. Still, you might consider it cleaner and more elegant to ship ebooks that have been freshly-generated and not exposed to iTunes.
On the subject of ePub validation, if you haven’t already done so it’s well-worth checking out Flightcrew, which is capable of finding many problems that epubcheck misses. The author has blogged about it here.